Gene interactions and pathways from curated databases and text-mining
Proc Natl Acad Sci U S A 2001, PMID: 11447289

Critical role for the docking-protein FRS2 alpha in FGF receptor-mediated signal transduction pathways.

Hadari, Y R; Gotoh, N; Kouhara, H; Lax, I; Schlessinger, J

The docking protein FRS2 alpha has been implicated as a mediator of signaling via fibroblast growth factor receptors (FGFRs). We have demonstrated that targeted disruption of FRS2 alpha gene causes severe impairment in mouse development resulting in embryonal lethality at E7.0--E7.5. Experiments with FRS2 alpha-deficient fibroblasts demonstrate that FRS2 alpha plays a critical role in FGF-induced mitogen-activated protein (MAP) kinase stimulation, phosphatidylinositol-3 (PI-3) kinase activation, chemotactic response, and cell proliferation. Following FGF stimulation, tyrosine phosphorylated FRS2 alpha functions as a site for coordinated assembly of a multiprotein complex that includes Gab1 and the effector proteins that are recruited by this docking protein. Furthermore, we demonstrate that different tyrosine phosphorylation sites on FRS2 alpha are responsible for mediating different FGF-induced biological responses. These experiments establish the central role of FRS2 alpha in signaling via FGFRs and demonstrate that FRS2 alpha mediates multiple FGFR-dependent signaling pathways critical for embryonic development.

Document information provided by NCBI PubMed

Text Mining Data

mitogen activated protein ( MAP ) kinase → FGF: " Experiments with FRS2 alpha-deficient fibroblasts demonstrate that FRS2 alpha plays a critical role in FGF induced mitogen activated protein ( MAP ) kinase stimulation, phosphatidylinositol-3 (PI-3) kinase activation, chemotactic response, and cell proliferation "

phosphatidylinositol-3 (PI-3) → FGF: " Experiments with FRS2 alpha-deficient fibroblasts demonstrate that FRS2 alpha plays a critical role in FGF induced mitogen activated protein ( MAP ) kinase stimulation, phosphatidylinositol-3 (PI-3) kinase activation, chemotactic response, and cell proliferation "

Manually curated Databases

  • IRef Hprd Interaction: PTPN11 — FRS2 (in vitro)
  • IRef Hprd Interaction: PTPN11 — FRS2 (in vivo)
  • IRef Ophid Interaction: FRS2 — PTPN11 (aggregation, confirmational text mining)
  • Reactome Reaction: FGF1 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF17 → GRB2 (reaction)
  • Reactome Reaction: FGFR3 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF5 → GRB2 (reaction)
  • Reactome Reaction: SOS1 → FRS3 (reaction)
  • Reactome Reaction: FGF3 → GRB2 (reaction)
  • Reactome Reaction: FGF18 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF9 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF7 → GRB2 (indirect_complex)
  • Reactome Reaction: FGFR1 → SOS1 (reaction)
  • Reactome Reaction: SOS1 → KLB (indirect_complex)
  • Reactome Reaction: FGF8 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF23 → GRB2 (reaction)
  • Reactome Reaction: FGF16 → SOS1 (reaction)
  • Reactome Reaction: FGF23 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF10 → SOS1 (indirect_complex)
  • Reactome Reaction: GRB2 → KL (indirect_complex)
  • Reactome Reaction: FGF8 → GRB2 (reaction)
  • Reactome Reaction: FGF1 → SOS1 (reaction)
  • Reactome Reaction: FGF8 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF19 → SOS1 (reaction)
  • Reactome Reaction: FGF10 → SOS1 (reaction)
  • Reactome Reaction: GRB2 → KLB (reaction)
  • Reactome Reaction: FGFR2 → SOS1 (reaction)
  • Reactome Reaction: FGF19 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF4 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF5 → GRB2 (indirect_complex)
  • Reactome Reaction: GRB2 → FRS3 (indirect_complex)
  • Reactome Reaction: FGF16 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF17 → GRB2 (indirect_complex)
  • Reactome Reaction: FGFR3 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF3 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF2 → GRB2 (reaction)
  • Reactome Reaction: FGFR2 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF10 → GRB2 (reaction)
  • Reactome Reaction: FGF6 → GRB2 (reaction)
  • Reactome Reaction: GRB2 → FGFR3 (indirect_complex)
  • Reactome Reaction: FGF1 → GRB2 (reaction)
  • Reactome Reaction: FGF20 → GRB2 (reaction)
  • Reactome Reaction: FGFR1 → GRB2 (reaction)
  • Reactome Reaction: SOS1 → FGFR2 (indirect_complex)
  • Reactome Reaction: FGF2 → SOS1 (reaction)
  • Reactome Reaction: FGF22 → SOS1 (reaction)
  • Reactome Reaction: GRB2 → KL (reaction)
  • Reactome Reaction: SOS1 → FGFR2 (reaction)
  • Reactome Reaction: FGFR2 → GRB2 (reaction)
  • Reactome Reaction: FGF18 → GRB2 (reaction)
  • Reactome Reaction: FGF6 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF7 → SOS1 (reaction)
  • Reactome Reaction: FGF18 → SOS1 (reaction)
  • Reactome Reaction: SOS1 → FRS2 (reaction)
  • Reactome Reaction: GRB2 → KLB (indirect_complex)
  • Reactome Reaction: FGFR4 → SOS1 (reaction)
  • Reactome Reaction: FGF22 → SOS1 (indirect_complex)
  • Reactome Reaction: GRB2 → FGFR2 (indirect_complex)
  • Reactome Reaction: GRB2 → FGFR2 (reaction)
  • Reactome Reaction: SOS1 → FRS2 (indirect_complex)
  • Reactome Reaction: FGF16 → GRB2 (reaction)
  • Reactome Reaction: FGFR1 → SOS1 (indirect_complex)
  • Reactome Reaction: GRB2 → FGFR3 (reaction)
  • Reactome Reaction: FGF18 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF19 → GRB2 (indirect_complex)
  • Reactome Reaction: SOS1 → FGFR3 (reaction)
  • Reactome Reaction: SOS1 → FRS3 (indirect_complex)
  • Reactome Reaction: FGF23 → GRB2 (indirect_complex)
  • Reactome Reaction: FGFR4 → GRB2 (reaction)
  • Reactome Reaction: FGF23 → SOS1 (reaction)
  • Reactome Reaction: FGFR4 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF20 → SOS1 (reaction)
  • Reactome Reaction: FGF5 → SOS1 (reaction)
  • Reactome Reaction: SOS1 → KL (reaction)
  • Reactome Reaction: FGFR4 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF22 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF8 → SOS1 (reaction)
  • Reactome Reaction: SOS1 → FGFR3 (indirect_complex)
  • Reactome Reaction: FGFR3 → GRB2 (reaction)
  • Reactome Reaction: GRB2 → FRS2 (reaction)
  • Reactome Reaction: GRB2 → FRS2 (indirect_complex)
  • Reactome Reaction: FGF4 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF7 → GRB2 (reaction)
  • Reactome Reaction: FGF3 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF16 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF2 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF9 → SOS1 (reaction)
  • Reactome Reaction: FGFR1 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF20 → SOS1 (indirect_complex)
  • Reactome Reaction: FGFR2 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF22 → GRB2 (reaction)
  • Reactome Reaction: FGF20 → GRB2 (indirect_complex)
  • Reactome Reaction: SOS1 → KLB (reaction)
  • Reactome Reaction: FGFR3 → SOS1 (reaction)
  • Reactome Reaction: FGF17 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF2 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF6 → SOS1 (reaction)
  • Reactome Reaction: FGF1 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF10 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF17 → SOS1 (reaction)
  • Reactome Reaction: FGF5 → SOS1 (indirect_complex)
  • Reactome Reaction: FGF9 → GRB2 (reaction)
  • Reactome Reaction: FGF3 → SOS1 (reaction)
  • Reactome Reaction: FGF6 → GRB2 (indirect_complex)
  • Reactome Reaction: FGF19 → GRB2 (reaction)
  • Reactome Reaction: FGF4 → GRB2 (reaction)
  • Reactome Reaction: GRB2 → FRS3 (reaction)
  • Reactome Reaction: FGF4 → SOS1 (reaction)
  • Reactome Reaction: FGF7 → SOS1 (indirect_complex)
  • Reactome Reaction: SOS1 → KL (indirect_complex)
  • Reactome Reaction: FGF9 → GRB2 (indirect_complex)
In total, 51 gene pairs are associated to this article in curated databases